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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 6 April, 2012 to 26 April, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-Propenoic acid, reaction products with dipentaerythritol
EC Number:
800-838-4
Cas Number:
1384855-91-7
Molecular formula:
Molecular formula not available for this UVCB.
IUPAC Name:
2-Propenoic acid, reaction products with dipentaerythritol
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): DPHA
- Substance type: Colourless to slightly yellow viscous liquid
- Physical state: Liquid
- Purity: UVCB, 100%
- Lot/batch No.: JBHA0020T
- Expiration date of the lot/batch: 06 March 2014
- Storage condition of test material: At room temperature protected from light
- Hygroscopic: No
- Volatile: No
- Test substance handling: Use amber-coloured glassware or wrap container in aluminium foil
- Specific Gravity / Density: 1.17 g/cm3
- Stability at higher temperatures: Yes, maximum temperature: 60⁰C. Maximum duration: 24 h

Test animals

Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8-9 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (first group: 156 - 178 g; second group: 149 - 157 g).
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 h after administration of the test substance. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 d

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approx 15 room air changes/h, and a 12-h light/12-h dark cycle.

IN-LIFE DATES: From 06 April 2012 to 26 April 2012

Administration / exposure

Route of administration:
oral: gavage
Details on oral exposure:
GAVAGE METHOD: Plastic feeding tubes.

Frequency: Single dosage, on Day 1.

VEHICLE Polyethylene glycol 400 (Merck, Darmstadt, Germany) (specific gravity 1.125).
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) bw.

DOSAGE PREPARATION:
The formulations (w/w) were prepared using amber coloured glassware within 4 h prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the test substance and vehicle. No correction was made for purity of the test substance.
Doses:
2000 mg/kg bw

No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and/or piloerection was noted in all animals on Day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
other: EU CLP criteria not met
Conclusions:
Under the study conditions, the oral LD50 value of the test substance in rats was considered to be > 2,000 mg/kg bw.
Executive summary:

A study was conducted to determine the acute oral toxicity of test substance, DPHA according to OECD Guideline 423, EU method B.1 tris, EPA OPPTS 870.1100 and Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF) Guidelines, in compliance with GLP. The test substance was administered by oral gavage to two groups of three female Wistar rats at 2,000 mg/kg bw. No mortality occurred. Hunched posture and/or piloerection were noted in all animals on Day 1. The body weight gain shown over the study period was similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post-mortem examination. Under the study conditions, the oral LD50 value of the test substance in rats was considered to be > 2,000 mg/kg bw (Beerens-Heijnen, 2012).

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